View source for 6isu


==Crystal structure of Lys27-linked di-ubiquitin in complex with its selective interacting protein UCHL3==
<StructureSection load='6isu' size='340' side='right'caption='[[6isu]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6isu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ISU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ISU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.866&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SLZ:L-THIALYSINE'>SLZ</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6isu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6isu OCA], [https://pdbe.org/6isu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6isu RCSB], [https://www.ebi.ac.uk/pdbsum/6isu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6isu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UCHL3_HUMAN UCHL3_HUMAN] Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3", and exhibits a preference towards 'Lys-48'-linked Ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. Required for stress-response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome and is associated with neurogenerative disorders.<ref>PMID:2530630</ref> <ref>PMID:9790970</ref> <ref>PMID:19154770</ref> <ref>PMID:21762696</ref> <ref>PMID:22689415</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
New synthetic strategies that exploited the strengths of both chemoselective ligation and recombinant protein expression were developed to prepare K27 di-ubiquitins (diUb), which enabled mechanistic studies on the molecular recognition of K27-linked Ubs by single-molecule Forster resonance energy transfer (smFRET) and X-ray crystallography. The results revealed that free K27 diUb adopted a compact conformation, whereas upon binding to UCHL3, K27 diUb was remodeled to an open conformation. The K27 isopeptide bond remained rigidly buried inside the diUb moiety during binding, an interesting unique structural feature that may explain the distinctive biological function of K27 Ub chains.

Chemical Protein Synthesis Enabled Mechanistic Studies on the Molecular Recognition of K27-linked Ubiquitin Chains.,Pan M, Zheng Q, Ding S, Zhang L, Qu Q, Wang T, Hong D, Ren Y, Liang L, Chen C, Mei Z, Liu L Angew Chem Int Ed Engl. 2019 Feb 25;58(9):2627-2631. doi: 10.1002/anie.201810814., Epub 2019 Jan 25. PMID:30589182<ref>PMID:30589182</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6isu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thioesterase 3D structures|Thioesterase 3D structures]]
*[[3D structures of ubiquitin|3D structures of ubiquitin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ding S]]
[[Category: Hong D]]
[[Category: Pan M]]
[[Category: Ren Y]]
[[Category: Zheng Q]]